A genome-wide significant linkage for severe depression on chromosome 3: the depression network study.

Gerome Breen, Bradley Webb, Amy Butler, Edwin van den Oord, Ferderica Tozzi, Nick Craddock, Michael Gill, A. Korszun, Wolfgang Maier, Lefkos Middleton, Ole Mors, Michael Owen, Sarah Cohen-Woods, Julia Perry, Nicholas Galwey, Ruchi Upmanyu, Ian Craig, Cathryn Lewis, Mandy Ng, Shyama BrewsterMartin Preisig, Marcella Rietschel, Lisa Jones, Jo Knight, John Rice, Pierandrea Muglia, Anne Farmer, Peter McGuffin

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    39 Citations (Scopus)

    Abstract

    Objective: The purpose of this study was to find loci for major depression via linkage analysis of a large sibling pair sample. Method: The authors conducted a genome-wide linkage analysis of 839 families consisting of 971 affected sibling pairs with severe recurrent major depression, comprising waves I and II of the Depression Network Study cohort. In addition to examining affected status, linkage analyses in the full data set were performed using diagnoses restricted by impairment severity, and association mapping of hits in a large case-control data set was attempted. Results: The authors identified genome-wide significant linkage to chromosome 3p25-26 when the diagnoses were restricted by severity, which was a maximum LOD score of 4.0 centered at the linkage marker D3S1515. The linkage signal identified was genome-wide significant after correction for the multiple phenotypes tested, although subsequent association mapping of the region in a genome-wide association study of a U.K. depression sample did not provide significant results. Conclusions: The authors report a genome-wide significant locus for depression that implicates genes that are highly plausible for involvement in the etiology of recurrent depression. Despite the fact that association mapping in the region was negative, the linkage finding was replicated by another group who found genome-wide-significant linkage for depression in the same region. This suggests that 3p25-26 is a new locus for severe recurrent depression. This represents the first report of a genome-wide significant locus for depression that also has an independent genome-wide significant replication.

    Original languageEnglish
    Pages (from-to)840-847
    Number of pages8
    JournalAmerican Journal of Psychiatry
    Volume168
    Issue number8
    DOIs
    Publication statusPublished - Aug 2011

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    Breen, G., Webb, B., Butler, A., van den Oord, E., Tozzi, F., Craddock, N., Gill, M., Korszun, A., Maier, W., Middleton, L., Mors, O., Owen, M., Cohen-Woods, S., Perry, J., Galwey, N., Upmanyu, R., Craig, I., Lewis, C., Ng, M., ... McGuffin, P. (2011). A genome-wide significant linkage for severe depression on chromosome 3: the depression network study. American Journal of Psychiatry, 168(8), 840-847. https://doi.org/10.1176/appi.ajp.2011.10091342